The University of Pennsylvania Research Center in Oral Biology is a broadly based multidisciplinary institute involving scientists mainly in the School of Dental Medicine but in which members of the Schools of Medicine and Veterinary Medicine also participate. the fundamental aim of the Center is to provide the setting and resources for scientists in a variety of disciplines to apply the latest scientific and technological advances to challenging oral health problems. The research program is organized under two major areas: (1) The Molecular and Cellular Biology of Oral Pathogens, (2) The Molecular and Cellular Biology of Mineralized Tissues. Included in the program are 4 research projects, and 2 supporting Cores. The problems under investigation range from studies on the molecular mechanisms involved in the pathogenesis or oral infections to delineation of the factors responsible for the differentiation of cells in mineralizing tissues. Specifically, we are continuing fundamental studies on the glycoproteins of Herpes Simplex virus, which remains a major public health problem, causing widespread morbidity and, because of its oncogenic potential, possibly even mortality. Center studies have led to clinical trials of a promising subunit vaccine based on glycoprotein gD. In the oral cavity, the aggregation of bacteria and their clearance or alternatively their colonization on tooth surfaces plays a central role in the initiation of both dental caries and periodontal disease. To understand the mechanisms of these interactions, detailed studies of the binding of streptococci through a surface receptor protein (that has been cloned) to a salivary agglutinin are being carried out. Progressive tissue destruction is the hallmark of periodontal disease, and studies continue on the fundamental mechanisms whereby the leukotoxin of Actinobacillus actinomycetemcomitans, a likely candidate as a major periodontal pathogen, kills host cells. During tooth formation, ameloblasts secrete proteins which are involved in mineralization of the enamel layer. Center scientists have cloned the genes encoding the major class of enamel protein, amelogenins, and studies are planned, using recombinantly expressed proteins, to determine their role in the formation of the unique hydroxyapatite crystals found in the developing enamel matrix. Many of these studies involved collaboration between scientists in the Center and also with other scientists within and outside the University. In addition to its research function, the Center serves as a resource for the training of undergraduate and graduate dental students, undergraduates in the College and Ph.D. candidates in the biological sciences.